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Borata-alkenes can serve as anionic olefin equivalent ligands in transition metal chemistry. A chelate ligand of this type is described and used for metal coordination. Deprotonation of the Mes2P(CH2)2B(C6F5)2 frustrated Lewis pair in the α-CH[B] position gave the methylene-bridged phosphane/borata-alkene anion. It reacted with the [Rh(nbd)Cl] or [Rh(CO)2Cl] dimers to give the respective neutral chelate [P/C[double bond, length as m-dash]B][Rh] complexes. The reaction of the [P/C[double bond, length as m-dash]B]- anion with [Ir(cod)Cl]2 proceeded similarly, only that the complex underwent a subsequent oxidative addition reaction at the mesityl substituent. Both the resulting Ir(iii)hydride complex 15 and the P/borata-alkene Rh system 12 were used as hydrogenation catalysts. The [P/C[double bond, length as m-dash]B(C6F5)2]Rh(nbd) complex 12 served as a catalyst for arylacetylene polymerization.

The discrimination of d-galactosamine (G), representative of the amino-sugar class of compounds, has been probed through nano-ESI-FT-ICR mass spectrometry by isolating the relevant [C·H·G]+ proton-bound complexes with the enantiomers of the cyclochiral resorcin[4]arene C and allowing them to react toward three primary amines (B = EtNH2, iPrNH2, and (R)- and (S)-sBuNH2). The system under investigation presents several features that help to unveil the behavior of unprotected G in such a supramolecular architecture: (i) the hydrophobic derivatization of the C convex side forces the polar guest G to be coordinated by the cyclochiral concave region; (ii) protonated d-galactosamine exists as an anomeric mixture, dynamically interconverting throughout the experimental time-window; and (iii) different basicities of B allow the experiment to subtly tune the reactivity of the [C·H·G]+ complexes. Three [C·H·G]+ aggregate-types were found to exist, differing in both their origin and reactivity. The most reactive adducts ([C·H·G]ESI+), generated in the electrospray environment, undergo a G-to-B ligand exchange in competition with a partial isomerization to the unreactive [C·H·G]GAS+-type complexes. Finally, the poorly reactive [C·H·G]SOL+ aggregates are formed in solution over an hours-long time scale. A cyclochirality effect on the reactivity was found to depend on the considered [C·H·G]+ aggregate-type.

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst–catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which reacts mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid–acid interactions have a drastic influence on the reaction rate and stereoselectivity of asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids., Supramolecular acid–acid interactions lead to competing monomeric and dimeric pathways in phosphoric acid catalysis – so that stereoselectivities depend on catalyst concentration.

Nitroxide-mediated polymerization (NMP) was applied to prepare alternating copolymers using 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) 1 and ((6-trimethylsilyl)-hex-5-yn-1-yl)vinyl ether (THVE) 2 as monomers. The alternating sequence of the resulting poly(HFIPA-alt-THVE) 3 was proved by using tandem mass spectrometry (MS/MS) and further supported by 1H NMR spectroscopy. Alternating alkyne and activated ester moieties of copolymer 3 were further functionalized with organic azides and amines using sequential Cu-catalyzed azide–alkyne click (CuAAC) and amidation reactions, providing dually functionalized poly(acrylamide-alt-triazole) polymers 5. Water-soluble alternating poly(acrylic acid-alt-triazole) copolymers 9 were obtained by saponification of HFIP esters. 1H and 19F NMR spectroscopy, IR spectroscopy as well as gel permeation chromatography (GPC) were used to characterize the polymers before and after functionalization.

Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22–69% yield with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21–50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and 13C NMR data.

Rationale Mycotoxins are toxic secondary metabolites produced by various fungi. Their distribution within contaminated material is of high interest to obtain insight into infection mechanisms and the possibility of reducing contamination during food processing. Methods Various vegetable foodstuffs were infected with fungi of the genera Fusarium and Aspergillus. The localization of the produced mycotoxins was studied by matrix-assisted laser desorption/ionization time-of flight mass spectrometry imaging (MALDI-MSI) of cryosections obtained from infected material. The results were confirmed by high-performance liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (HPLC/MS/MS). Results The mycotoxins ochratoxin A (OTA) and fumonisins of the B- and C-series (FB1, FB2, FB3, FB4, FC1, FC2/3, and FC4) as well as partially hydrolyzed fumonisins (pHFB1, pHFB2, pHFB3, pHFC1, and pHFC2/3) could successfully be detected by MALDI-MSI in mold-infested foodstuffs. The toxins are distributed differently in the material: OTA is co-localized with visible fungal spoilage while fumonisins could be detected throughout the whole sample. Conclusions This work shows the applicability of MALDI-MSI to mycotoxin analysis. It has been demonstrated that the analyzed mycotoxins are differently distributed within moldy foodstuffs. These findings show the potential of MALDI-MSI for the localization of these hazardous compounds in various plant tissues. Copyright © 2016 John Wiley & Sons, Ltd.

The electrospray ionization-collision-induced dissociation mass spectra of nine pyrogallol tribenzyl ethers, 2-10, and a catechol dibenzyl ether, 11, that bear various functional groups or larger structural extensions have been studied with respect to the occurrence of a highly characteristic consecutive loss of two benzyl radicals from the sodiated molecular ions, [M + Na](+). It is shown that this specific fragmentation reaction strongly dominates other fragmentation routes, such as loss of carbon monoxide, formaldehyde and water. In addition, elimination of benzaldehyde occurs as a minor fragmentation channel in most cases. In contrast to these aryl-benzyl ethers, the consecutive two-fold loss of C7H7 center dot is suppressed in the [M + Na](+) ions of dibenzyl ethers derived from multiply benzylated gallocatechin and catechin, where the elimination of benzyl alcohol prevails the primary fragmentation almost completely. The secondary fragmentation of the [M + Na](+) ions, which also comprises the two-fold loss of C7H7 center dot, as well as a remarkable primary fragmentation of a flavene-based congener leading to particularly stable sodium-free chromylium product ions is also presented.

SummaryNeuronal information processing requires a large amount of energy, indicating that sugars and other metabolites must be efficiently delivered. However, reliable neuronal function also depends on the maintenance of a constant microenvironment in the brain. Therefore, neurons are efficiently separated from circulation by the blood-brain barrier, and their long axons are insulated by glial processes. At the example of the Drosophila brain, we addressed how sugar is shuttled across the barrier to nurture neurons. We show that glial cells of the blood-brain barrier specifically take up sugars and that their metabolism relies on glycolysis, which, surprisingly, is dispensable in neurons. Glial cells secrete alanine and lactate to fuel neuronal mitochondria, and lack of glial glycolysis specifically in the adult brain causes neurodegeneration. Our work implies that a global metabolic compartmentalization and coupling of neurons and glial cells is a conserved, fundamental feature of bilaterian nervous systems independent of their size.

A CuII hydrazone complex has been synthesized that can be reduced in situ in boiling methanol to give the corresponding CuI complex. The latter complex readily activates dioxygen under ambient conditions, as was unambiguously shown by isotopic labeling studies. As a consequence of the dioxygen activation, the thienyl moiety appended to the hydrazone ligand is easily oxidized in β position (C–H C–O), finally leading to a change in the coordination environment of the central metal ion. All relevant complexes have been structurally characterized by single-crystal X-ray diffraction analyses. The hydrazone ligand applied in this study does not mimic a biologically relevant coordination motif in copper-containing oxygenases. Nonetheless, the reactivity of the CuI complex resembles that found in many oxygenases, indicating that hydrazone ligands may be well-suited for the generation of novel bioinspired oxidation catalysts.

The successive loss of two benzyl radicals from the [M + Na] + ions of the isomeric dihydroxybenzene dibenzyl ethers ( 2 – 4 ) and of the isomeric trihydroxybenzene tribenzyl ethers ( 5 – 7 ) under ESI/CID conditions has been studied by deuterium labelling, MS n experiments and DFT calculations. The fragmentation of the [M + Na] + ions of 2 and 4 consists exclusively of the consecutive losses of two C 7 H 7 (benzyl) radicals. This process is largely suppressed in the corresponding [M + Na] + ions of the meta isomer 3 and also in those of the 1,3,5-analog, phloroglucinol tribenzyl ether ( 6 ), suggesting the facile formation of sodiated ortho - and para -quinone ions, [C 6 H 4 O 2 + Na] + , in the cases of 2 and 4 , respectively. This finding is corroborated by a detailed investigation of the sodiated tribenzyl ethers of pyrogallol, [ 5 + Na] + , and 1,2,4-trihydroxybenzene, [ 7 + Na] + , and their isotopologs bearing differently labelled benzyl residues. Again, the successive loss of two C 7 H 7 radicals is the only fragmentation channel for ions [ 7 + Na] + and strongly predominates for ions [ 5 + Na] + , with the primary and secondary losses being highly regiospecific: ions [ 5 + Na] + lose the first benzyl residue almost exclusively from the central position ( O -2) and only then a lateral C 7 H 7 radical (from O -1 or O -3). Surprisingly, the very minor primary loss of a lateral benzyl group is followed by that of the other lateral one, suggesting a two-step isomerization process initiated by a 1,4-H shift. Ions [ 7 + Na] + lose the first benzyl radical almost exclusively from O -1, in very minor amounts from O -2 but not at all from O -4. The secondary loss of C 7 H 7 subsequent to the major primary loss occurs from both O -2 and O -4 in similar amounts, reflecting the relative stabilities of the sodiated benzyloxy-substituted ortho - and para -benzoquinones. This and several other details of the energy profiles associated with the twofold benzyl loss from ions [ 5 + Na] + and [ 7 + Na] + were calculated by use of the DFT methodology and were found to agree very well with the regioselectivities observed. Finally, the pyrogallol-based ions [ 5 + Na] + were found to eliminate benzaldehyde in minor but significant relative amounts, which takes place with high regioselectivity from O -1 or O -3.

2-Heptyl-4-hydroxyquinoline N-oxide (HQNO), a major secondary metabolite and virulence factor produced by the opportunistic pathogen Pseudomonas aeruginosa, acts as a potent inhibitor of respiratory electron transfer and thereby affects host cells as well as microorganisms. In this study, we demonstrate the previously unknown capability of environmental and pathogenic bacteria to transform and detoxify this compound. Strains of Arthrobacter and Rhodococcus spp. as well as Staphylococcus aureus introduced a hydroxyl group at C-3 of HQNO, whereas Mycobacterium abscessus, M. fortuitum, and M. smegmatis performed an O-methylation, forming 2-heptyl-1-methoxy-4-oxoquinoline as the initial metabolite. Bacillus spp. produced the glycosylated derivative 2-heptyl-1-(β-d-glucopyranosydyl)-4-oxoquinoline. Assaying the effects of these metabolites on cellular respiration and on quinol oxidase activity of membrane fractions revealed that their EC50 values were up to 2 orders of magnitude higher than that of HQNO. Furth...

Tenoxicam and lornoxicam are nonsteroidal anti-inflammatory drugs, were subjected to photoirradiation at 254 nm led to the photodegradation of the pharmaceutical agents. Both, the isolated photodegradation products and the pharmaceutical agents were examined toward DNA binding and degradation. The photodegradation products degrade calf thymus in concentration dependent manner.

The unidirectional triple-hydrogen (3H) rearrangement of the radical cations of 3-aryl-1-propanols bearing an electron-rich substitutent in the para-position was investigated for the diastereomeric 2-(4-dimethylamino)benzylcyclohexanols and 2-(4-dimethylamino)-benzylcyclopentanols and confirmed to be a highly stereospecific feature. Whereas the standard electron ionization (EI) (70 eV) mass spectra of the trans-isomers exhibit very minor (∼ 2%–3%) albeit stereospecific peaks for the relevant C8H13N•+ ions ( m/z 123), the metastable ion [mass-analyzed ion kinetic energy (MIKE)] spectra show these peaks with significant relative intensity (8%–17%). The respective cis-isomers do not undergo the 3H rearrangement, be it under standard or under metastable-ion conditions. The stereospecific 3H rearrangement is suppressed in the radical cations of cis- and trans-3-(4-dimethylamino)phenylcyclohexanol, the mass and MIKE spectra of which are governed by cleavage processes of the cyclohexane ring, which impedes the stereochemical assignment of the isomers by mass spectrometry. A multistep mechanism for the unidirectional 3H rearrangement is discussed in view of the present and previous experimental data.

The fragmentation reactions of the molecular ion of the three isomeric methylpyridines (2-picoline 1, 3-picoline 2, and 4-picoline 3) were studied using methods of tandem mass spectrometry and quantum chemical calculations with Gaussian-3 (G3) theory using the B3LYP density functional method (G3//B3LYP). Additionally RRKM calculations of the microcanonical rate constants of selected reaction pathways were performed. Derivatives of 2- and 4-picoline which bear an isotopically labeled methyl substituent (CD3: 1-d(3) and 3-d(3), (CH3)-C-13: 1-C-13 and 3-C-13) were also analyzed. Of the four primary dissociation reactions of the picoline radical cations 1(center dot+)-3(center dot+), the loss of a hydrogen atom, the elimination of an ethyne molecule and the elimination of a hydrogen cyanide molecule are observed in the MIKE spectra, while the loss of a methyl radical is only found in the collisional activation (CA) mass spectra of the molecular ions. The CA mass spectra of the labeled picoline radical ions reveal that some positional hydrogen exchange and carbon exchange takes place before the loss of the methyl radical. According to the G3 and RRKM calculations, the direct cleavage of the methyl substituent competes effectively with increasing internal energy of the ion with the loss of a methyl radical after rearrangements. The other three pathways found for metastable molecular ions are accompanied by efficient or complete hydrogen scrambling. The theoretical calculations prove that this scrambling occurs mainly by initial H-transfer from the methyl group to the pyridine ring and a subsequent H-ring walk. The calculations show further, that loss of H-center dot may occur from many of the intermediate ions after the rearrangements but that the direct loss of H-center dot from the methyl substituent competes successfully even at low energies, contrary to the behavior of the toluene radical ion. The elimination of an ethyne molecule gives rise to a broad flat-topped signal in the mass-analyzed ion kinetic energy (MIKE) spectra, and the MIKE spectra of 1-C-13 and 3-C-13 exhibit a 1:1 sharing of the C-13-label between ionic and neutral products. These particular features are explained by the theoretical calculations by a first rearrangement of the picoline radical cations to a seven-membered aza-cycloheptatriene radical cation 4(center dot+) followed by a rearrangement to a more rigid bicyclo-[3.2.0] isomer before the elimination of ethyne. Finally, the elimination of a hydrogen cyanide molecule exhibits only minor loss of C-13-label in the case of 1-C-13 and 3-C-13. This observation does not agree with any mechanism including a rearrangement to 4(center dot+). The theoretical calculations suggest that instead the loss of the hydrogen cyanide molecule proceeds by a cleavage of the pyridine ring after the initial H-transfer from the methyl substituent Although this pathway needs more energy than a rearrangement to 4(center dot+), its rate coefficients are superior owing to its loose transition states. (C) 2012 Elsevier B.V. All rights reserved.

Mycotoxins are toxic secondary metabolites produced by various fungi. Their distribution within contaminated material is of high interest to obtain insight into infection mechanisms and the possibility of reducing contamination during food processing.Various vegetable foodstuffs were infected with fungi of the genera Fusarium and Aspergillus. The localization of the produced mycotoxins was studied by matrix-assisted laser desorption/ionization time-of flight mass spectrometry imaging (MALDI-MSI) of cryosections obtained from infected material. The results were confirmed by high-performance liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (HPLC/MS/MS).The mycotoxins ochratoxin A (OTA) and fumonisins of the B- and C-series (FBThis work shows the applicability of MALDI-MSI to mycotoxin analysis. It has been demonstrated that the analyzed mycotoxins are differently distributed within moldy foodstuffs. These findings show the potential of MALDI-MSI for the localization of these hazardous compounds in various plant tissues. Copyright © 2016 John WileySons, Ltd.

A novel [2]catenane was synthesised by ring-closing metathesis from a Ca-bisphosphate template. The resulting interlocked structure features two chiral 1,1′-binaphthyl-phosphates, leading to a bifunctional catenane structure. Initial binding studies point at the applicability of such mechanically interlocked bisphosphates as artificial receptors for dicationic guest molecules.

An electron ionisation study on the fragmentation of metastable molecular radical cations of ethyl 3-phenylpropanoate (ethyl dihydrocinnamate) and related arylalkanoic acid esters was performed by mass-analysed ion kinetic energy (MIKE) spectrometry. Six deuterium-labelled isotopomers of ethyl dihydrocinnamate were synthesised and studied by MIKE spectrometry. The fragmentation leading to ions C7H7O+ (m/z 107) involving migration of the alkoxycarbonyl group was also observed in the 70-eV mass spectra of related alkyl dihydrocinnamates, but it was found to be a high-energy process that does not compete at low energies in metastable molecular ions. Instead, the metastable ions of ethyl dihydrocinnamate undergo competing losses of carbon monoxide, ethanol and the combined loss of these neutral fragments, giving ionised styrene, C8H8•+ (m/z 104). A highly specific H/D interchange involving the four hydrogen atoms at the benzylic α- and ortho-positions was found to precede the losses of ethanol and [ethanol + CO]. This represents another striking case of complete 4H – scrambling that enables the molecular ion to fully equilibrate the interchanging hydrogen atoms prior to fragmentation. A mechanism rationalising these observations and extending previously suggested mechanisms is proposed involving a series of distonic ions and the intermediacy of an ion/neutral complex. The metastable ions of the related esters exhibit in part similar fragmentation behaviour, but the McLafferty reaction turns out to be more favourable with higher alkyl dihydrocinnamates. For example, n-propyl 3-phenylpropanoate and isopropyl 3-phenylpropanoate react through highly distinct fragmentation channels.

The effect of cyclochirality of rccc-2,8,14,20-tetra-n-decyl-4,10,16,22-tetra-O-methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano-electrospray ionization (nano-ESI)-Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton-bound [C center dot H center dot G](+) complexes by nano-ESI of solutions containing an equimolar amount of quasi-enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision-induced dissociation experiments on some of the relevant [C-2 center dot H center dot G](+) three-body species and Density functional theory (DFT) calculations performed on the most selective systems. Copyright (C) 2012 John Wiley & Sons, Ltd.

N -Benzylpyridinium ions bearing an alkyl group at the pyridine nucleus were studied as potential precursors of gaseous ion/neutral complexes. The occurrence of I/N complexes [C 6 H 5 CH 2 + ··· alkylpyridine] was probed by the reactivity of the potential benzylic hydride donor sites present in the ortho- , meta- and para- alkyl groups (R = methyl, ethyl, isopropyl and benzyl). Collision-induced dissociation of the ions, carried out in an electrical ion cage mass spectrometer, revealed that hydride transfer strongly depends both on the energy requirements of the hydride transfer but also on the position of the hydride donor. Hydride transfer, giving rise to the loss of toluene, was found to occur exclusively with those N -benzylpyridinium ions which bear an isopropyl or a benzyl substituent in the ortho position of the pyridine ring, thus reflecting the intermediacy of I/N complexes. All of the putative hydride donor alkyl groups were found to be non-reactive in the meta and para positions, as were methyl and ethyl groups even in the ortho positions. Density functional calculations (B3LYP/6-311+G/3d,2p)//(B3LYP/6-31+G(d)) on the hydride-transfer and simple-cleavage channels were carried out to help rationalizing these observations. The results suggest that the intra-complex hydride abstraction from the 3- and 4-isopropyl- and from the 3- and 4-benzylpyridine neutrals, although being thermodynamically favorable, is suppressed by substantial intra-complex rotational (or reorientation) barriers.

The tetrabenzylated catechin 9 was prepared by benzylation of the commercially available pure (+)-catechin (3) and coupled with the commercially unavailable pentabenzylated (-)-gallocatechin 10, prepared in a one-step Mitsunobu-type cyclization of the triol 8 The highly stereoselective synthesis of benzylated prodelphinidins - catechin-(4 alpha -> 8)-gallocatechin (13), gallocatechin-(4 alpha -> 8)-gallocatechin (14), and gallocatechin-(4 alpha -> 8)-catechin (15) - is reported for the first time. The ESI(+)-CID mass spectra of the coupling products were found to feature regioselective retro-Diels-Alder (RDA) reactions and unusual sequential losses of pairs of C7H7 radicals (182 u) from the Na+ adduct ions

We report the unimolecular decomposition following collisional activation of protonated mono-, di- and trimethylbenzenes as a function of collision energy. The resulting energy-resolved mass spectra are then used for the quality control of high-level quantum chemical models of the respective potential energy surfaces. Distinction is made between direct dissociation products (CH4 or H2) and indirect products (alkenes), since formation of the latter requires extensive rearrangement of the molecular skeleton. Very good consistency was found between model and experiment. The models thereby provide a solid foundation for discussing the reaction mechanisms of the industrial methanol-to-hydrocarbon process. The losses of CH4, C2H4 and C3H6 from mesitylenium ions have been studied by 13C and 2H labelling and the alkene losses were found to occur via irreversible isomerisation pathways.

Motivation: High-resolution mass spectrometry (MS) is among the most widely used technologies in metabolomics. Metabolites participate in almost all cellular processes, but most metabolites still remain uncharacterized. Determination of the sum formula is a crucial step in the identification of an unknown metabolite, as it reduces its possible structures to a hopefully manageable set. Results: We present a method for determining the sum formula of a metabolite solely from its mass and the natural distribution of its isotopes. Our input is a measured isotope pattern from a high resolution mass spectrometer, and we want to find those molecules that best match this pattern. Our method is computationally efficient, and results on experimental data are very promising: for orthogonal time-of-flight mass spectrometry, we correctly identify sum formulas for >90% of the molecules, ranging in mass up to 1000 Da. Availability: SIRIUS is available under the LGPL license at http://bio.informatik.uni-jena.de/sirius/ Contact: anton.pervukhin@minet.uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online.

A variety of conformations for three model calix[4]arenes with 8 or 12 OH groups have been investigated by calculations at density functional (RI-BP86) and RI-MP2 level of approximation. The calixarenes form stable complexes with the alkali metal cations of lithium up to caesium. For the investigations all-valence electron basis sets as well as various effective core potentials were probed. The stabilities of complexes were analysed in comparison with the corresponding benzene complexes, M(+)center dot C6H6. The formation of the calixarene metal complexes is considered in two steps, (a) in a distortion from the equilibrium conformation of the free calixarenes and (b) subsequent complexation. The distortion energies are small for the 'crown' and larger for the 'boat' conformations. On the other hand the latter are more stabilized by significant interaction energy of the cation with two adjacent pi-systems of the aromatic rings. As a result, these two conformations are of similar stabilities for K+ to Cs+ complexes with resorc[4]arenes, with a slight advantage for the 'boat' structure. The most stable conformation for the coordination products of these cations with the calix[4]arene with 12 OH groups is a slightly flattened 'crown' that is derived by maximum hydrogen bonding of the OH-groups and the most effective cation-pi interactions. Special cases are complexes of Li+ and Na+ which in most instances prefer the coordination on the oxygen atoms of the upper rim of the calixarene cavities and thus form 'boat'-like structures. (c) 2005 Published by Elsevier B.V.

O-linked oligosaccharide groups ranging from di- to hexasaccharide were beta-eliminated by mild alkaline treatment under reducting conditions from the peptidogalactomannan of Aspergillus fumigatus mycelial cell wall. The resulting reduced oligosaccharides, which were the minor components of the peptidogalactomannan fraction, were fractionated to homogeneity by successive gel filtration and high-performance liquid chromatography. Their primary structures were determined based on a combination of techniques including gas chromatography, ESI-QTOF-MS, H-1 COSY and TOCSY, and H-1-C-13 HMQC NMR spectroscopy and methylation analysis, to be: alpha-Glcp-(1 --> 6)-Man-ol, beta-Galf-(1 --> 6)-alpha-Manp-(1 --> 6)-Man-ol, beta-Galf-(1 --> 5)-beta-Galf-(1 --> 6)-alpha-Manp-(1 --> 6)-Man-ol and beta-Galf-(1 --> 5)-[beta-Galf-(1 --> 5](3)-beta-Galf-(1 --> 6)-Man-ol. The beta-Galf containing oligosaccharides have not been previously described as fungal O-linked oligosaccharides. The peptidogalactomannan is antigenic and was recognized by human sera of patients with aspergillosis when probed by ELISA, but de-O-glycosylation rendered a 50% decrease in its reactivity. Furthermore, when tested in a hapten inhibition test, the isolated oligosaccharide alditols were able to block, on a dose-response basis, recognition between human sera and the intact peptidogalactomannan. The immunodominant epitopes were present in the tetra- and hexasaccharide, which contain a beta-Galf-(1 --> 5)-beta-Galf terminal group. These results suggest that the O-glycosidically linked oligosaccharide chains, despite being the less abundant carbohydrate component of the A. fumigatus peptidogalactomannan, may account for a significant part of its antigenicity, other than the known activity associated with the galactomannan component.

Resorc[4]arenes are compounds with interesting properties, mainly because of their ability to form host-guest complexes with the guest located inside the cavity. The size of the guest limits the complexation, as shown by a competition experiment with tetraalkylammonium ions of different size. By electroscopy lionization tandem mass spectrometric experiments on resorc[4]arene heterodimers bearing an alkali metal ion as guest, it was found that there must be two different binding mechanisms for alkali metal ions with high surface charge density (Li+ and Na+) on the one hand compared with those with a lower surface charge density on the other hand (K+, Rb+, Cs+). Copyright (C) 2001 John Wiley Sons, Ltd.

Physiologically relevant free fatty acids (FFAs) were analyzed by UV-laser desorption/ionization orthogonal extracting time-of-flight mass spectrometry (LDI-oTOF-MS). Dissected wings from Drosophila melanogaster fruit flies were used as the hydrophobic, laser energy strongly absorbing sample substrates. Using untreated substrates produces predominantly molecular [M + K](+) ions of the FFAs, whereas other alkali metal adducts can be generated by treating the wings with the corresponding alkali hydroxide before spotting of analyte. Limits of detection for the positive ion mode were determined for mixtures of isolated FFAs to values in the low 10 pmol range. Specific values depend on chain length and degree of unsaturation. R(2) coefficients for the analysis of saturated FFAs were found to be generally close to 0.98 over about 3 orders of magnitude if an internal standard (15:0 FFA) was added. Semiquantitative analyses of mixtures containing unsaturated FFAs are also possible but require more effort on the calibration strategy. Notably, both saturated and (poly-)unsaturated FFAs are detected sensitively in the presence of relatively high concentrations of other physiologically abundant lipids (phospholipids and triacyclglycerols). This simplifies screening of the FFA composition in crude tissue extracts. This feature is demonstrated by the analysis of a crude liver extract and that of fingermarks.

Objective Diadenosine polyphosphates (AP n As, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. Diadenosine pentaphosphate (AP 5 A) and diadenosine hexaphosphate (AP 6 A) are more potent than diadenosine tetraphosphate (AP 4 A) and diadenosine triphosphate (AP 3 A) and cause skeletal muscle vasoconstriction in rats. Little is known about their physiological and pathophysiological significance in humans. The aims of the present study were to compare thrombocyte AP n A concentrations in patients with essential hypertension (HYP) and in healthy normotensive humans (CON) using a novel quantitative assay and to assess a possible relationship between thrombocyte AP n A concentrations and skeletal muscle vascular resistance. Design and methods We describe a novel assay for quantification of AP n As in human platelets, involving platelet isolation from human blood, a solid-phase extracting procedure with a derivatized resin, desalting and quantitative determination of the substances with an ion-pair reversed-phase high-performance liquid chromatography (HPLC) system. The structural integrity of the isolated AP n As was confirmed by mixed assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) measurements and co-elution with added standards. The detection threshold for all four AP n As was 1 pmol/l and the inter-assay coefficients of variation were < 11% (n = 12). After venous blood sampling, mean arterial blood pressure (MAP) and forearm blood flow (FBF, using venous occlusion plethysmography) were measured in HYP and CON. Forearm vascular resistance (FVR) was calculated as MAP/FBF. Results HYP (n = 15) and CON (n = 15) did not significantly differ in platelet AP 3 A and AP 4 A content, but HYP had significantly higher thrombocyte concentrations of AP 5 A (56 ± 7 versus 32 ± 3 ng/μg β-thromboglobulin, P= 0.003) and AP 6 A (10 ± 1 versus 6 ± 1 ng/μg β-thromboglobulin, P = 0.015) than CON. HYP had significantly elevated FVR (50 ± 6 versus 33 ± 2 arbitrary units, P = 0.01) compared to CON. Significant correlations were found between AP 5 A and FVR (p = 0.38, P = 0.04) as well as between AP 6 A and FVR (p = 0.42, P = 0.02). In contrast, there were no significant correlations between AP n As and MAP. Conclusions The study shows that thrombocyte concentrations of AP 5 A and AP 6 A are elevated in patients with essential hypertension. Vasoconstriction caused by release of AP 5 A and AP 6 A from thrombocytes may contribute to the increase of vascular resistance in hypertensive patients.

rccc-2,8,14,20-Tetra- n-octyl-5,11,17,23-tetrahydroxyresorc[4]arene has the property to form cluster ions in both positive- and negative-ion mode with good intensity without the addition of any modifiers such as cesium. These cluster ions may be used for the calibration of electrospray mass spectrometers in the mass range up to m/z 6000.

A theoretical investigation has been carried out at the DFT ( B3LYP, RI-BP86, RI-B97-D) and RI-MP2 levels of approximation for octahydroxy-pyridine[4]arene and a series of its adducts with anions (BF4-, PF6-, NO3-, CH3COO- and CF3COO-) and ammonium cations (NH4+). The encapsulated complexes ( two hosts to one guest molecule) are predicted to be more stable in the gas phase than the corresponding 1 : 1 adducts. Calculations using Grimme's B97-D functional have provided relative energies, which agree well with those derived at the RI-MP2 level of theory. By taking solvent effects into account using the COSMO routine, the formation of the anionic adducts is significantly less favourable. Complexes of octahydroxy-pyridine[4]arene with the ammonium cation seem to be unstable in solution. The most promising complexes of octahydroxy-pyridine[4]arene with BF4- and PF6- have been studied experimentally. Only formation of 1 : 1 anionic adducts has been detected using electrospray ionization mass spectrometry. Probably, in the 1 : 1 complexes the coordinated anion still interacts with a counterion. The excess of anionic guests used in the experiment and the conditions in the ESI source of the mass spectrometer have been considered another possible reason for shifting the equilibrium towards the 1 : 1 aggregates.

This review describes the state-of-art in the field of the gas-phase reactivity of diastereomeric complexes formed between a chiral artificial receptor and a biologically active molecule. The presented experimental approach is a ligand-displacement reaction carried out in a nano ESI-FT-ICR instrument, supported by a thermodynamic MS-study and molecular-mechanics and molecular-dynamics (MM/MD) computational techniques. The noncovalent ion–molecule complexes are ideal for the study of chiral recognition in the absence of complicating solvent and counterion effects.

This review describes the state-of-art in the field of the gas-phase reactivity of diastereomeric complexes formed between a chiral artificial receptor and a biologically active molecule. The presented experimental approach is a ligand-displacement reaction carried out in a nano ESI-FT-ICR instrument, supported by a thermodynamic MS-study and molecular-mechanics and molecular-dynamics (MM/MD) computational techniques. The noncovalent ion–molecule complexes are ideal for the study of chiral recognition in the absence of complicating solvent and counterion effects.

The gas-phase encounters between 2-aminobutane and proton-bound chiral resorcin[4]arene/nucleoside complexes behave in the gas phase as supramolecular "chiroselective logic gates" by releasing the nucleoside depending on the resorcin[4] arene and the 2-aminobutane configurations.

The fragmentation of gaseous ion/neutral complexes [R+⋯C6H5CH2CH2CH2C6H4–R′] with (i) R = R′ = C4H9, (ii) R = C4H9 and R′ = CH3 and (iii) R = C6H11 and R′ = H has been studied by CI(CH4)-MIKE spectrometry of the corresponding alkyl-substituted 1,3-diphenylpropanes. Different from all other isomers containing two para-alkyl substituents, the [M+H]+ ion generated from the symmetrical ion [(4-tert-C4H9-C6H4)CH2CH2CH2(C6H4-4-tert-C4H9) + H]+ shows the characteristic fragmentation pattern of ion–neutral complexes containing a meta-alkyl-substituted 1,3-diphenylpropane. This indicates a proton-induced 1,2-shift of one or even both of the tert-C4H9 groups and requires the presence of the meta-(tert-C4H9)-substituted diphenylpropane as the neutral constituent of the eventually fragmenting I/N complex. As a consequence, it appears that the reactive complex [C4H9+⋯C6H5CH2CH2CH2(C6H4-3-tert-C4H9)] is formed prior to the generation of the expected “para-isomer”, [C4H9+⋯C6H5CH2CH2CH2(C6H4-4-tert-C4H9)]. Isobutyl analogues, such as [(4-iso-C4H9-C6H4)CH2CH2CH2(C6H4-4-iso-C4H9) + H]+, do not show evidence for the intermediacy of “isomerized” I/N complexes containing a tert-C4H9+ ion. The fragmentation of ion–neutral complexes containing C6H11+ ions, formed from the [M+H]+ ions of (4-cyclohexyl)- and of 4-(1-methylcyclopentyl)-substituted 1,3-diphenylpropane, indicate that the C6H11+ ions only partially retain their structural identity: while the secondary isomer, (CH2)5 > CH+, predominantly transfers a proton in competition to hydride abstraction, indicating its stronger Bronsted acidity, the tertiary isomer, (CH2)4 > C+CH3, mainly reacts by hydride abstraction. In spite of the partial isomerization, deuterium labelling experiments corroborate the usual regioselectivity of the hydride abstraction from the benzylic methylene groups in both cases.

The stereoselectivity of the reaction between (R)-(-)-2-butylamine and the diastereomeric proton-bound complexes of (+)-catharanthine (C) or (-)-vindoline (V) with some chiral amido[4]resorcinarenes has been investigated in the gas phase by ESI-FT-ICR-MS. The reaction stereoselectivity (0.56 < k(homo)/k(hetero) < 16.9) is found to depend critically on the functional groups present in the chiral pendants of the hosts. Rationalisation of the kinetic results is based on careful computational and spectroscopic studies of the most stable conformations of (+)-catharanthine and its protonated form in the isolated state and in water, as well as in a representative host structure. The emerging picture points to the relevant diastereomeric proton-bound complexes as quasi-degenerate, thus suggesting that their stereoselectivity in the guest exchange reaction is mostly due to kinetic factors. The results of this study may represent a starting point for a deeper comprehension of the intrinsic factors that endow these molecules, and their dimeric forms, with their biochemical properties.

The displacement processes of several guests, incorporated in a calixarene host system, were investigated in the gas phase by electrospray ionization-Fourier transform-ion cyclotron resonance (ESI-FT-ICR) mass spectrometry. The complexes resulting from a resorcin[4]arene host with ammonia and sec-butylamine guests were isolated in an ICR-cell, separately using both states of the photos-witch as well as two reference systems for the open and closed forms of the photoswitchable host. The isolated complexes were forced to exchange the guest by using methylamine, ethylamine and sec-butylamine, resulting in different reaction rates for all the measured systems. Especially, the reaction rates of both states of the photoswitch are dependent on the provided guest. Potential side effects like proton exchanges were examined by an H/D-exchange experiment. The results were investigated and supported by quantum chemical calculations (DFT). Copyright (C) 2008 John Wiley & Sons, Ltd.

Metal-directed self-assembly of a terpyridyl-functionalized cavitand yields a large hexameric coordination cage. (C) 2008 Elsevier Ltd. All rights reserved.

On the research avenue opened by the rigidified double-spanned resorcin[4]arene 1, we have synthesized both enantiomers of the two chiral basket resorcin[4]arenes 3 and 4, each containing two 1,2-diaminocyclohexane and 1,2-diphenylethylenediamine bridges, respectively. In the new compounds, the aromatic rims assume the expected flattened cone arrangement, whereas two different conformations, tentatively designated as "open wings" and "folded wings", were attributed to the bridge substituents according to molecular modeling studies. In MSn (ESI) experiments, the proton-bonded diastereomeric [4.H.A](+) complexes with amino acidic guests (A) exhibited a pronounced selectivity towards the enantiomers of tyrosine methyl ester (tyr(OMe)) and amphetamine (amph), whereas the chirality of tryptophan (trp) was ineffective. Moreover, a kinetic study on the base-induced displacement of the guest revealed that the L-tyr(OMe) (and L-amph) enantiomer is faster displaced from the heterochiral [4.H.L-tyr(OMe)](+) (or [ent-4.H.L-amph](+)) complex than from the homochiral [ent-4.H.L-tyr(OMe)](+) (or [4.H.L-amph](+)) one. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007.

Host-guest complexes of tetramethylcavitand with different ammonium cations were investigated by using a quantum chemical method at the density func tional level (BP86, B3LYP). The NH4+ cation is strongly bound to the host. Increasing creasing methyl substitution at the cation decreases its inclination towards the complex formation. The calculated data are in line with results from electrospray ionization mass spectrometry (ESI-MS) experiments. They reveal stable aggregates only for the NH4+ cation and for the primary alkylammonium cations.

The unimolecular reactions of radical cations and cations derived from phenylarsane, C6H5AsH2 (1) and dideutero phenylarsane, C6H5AsD2 (1-d2), were investigated by methods of tandem mass spectrometry and theoretical calculations. The mass spectrometric experiments reveal that the molecular ion of phenylarsane, 1(.+), exhibits different reactivity at low and high internal excess energy. Only at low internal energy the observed fragmentations are as expected, that is the molecular ion 1(.+) decomposes almost exclusively by loss of an H atom. The deuterated derivative 1-d2 with an AsD2 group eliminates selectively a D atom under these conditions. The resulting phenylarsenium ion [C6H5AsH](+), 2(+), decomposes rather easily by loss of the As atom to give the benzene radical cation [C6H6](.+) and is therefore of low abundance in the 70 eV EI mass spectrum. At high internal excess energy, the ion 1(.+) decomposes very differently either by elimination of an H-2 molecule, or by release of the As atom, or by loss of an AsH fragment. Final products of these reactions are either the benzoarsenium ion 4(.+), or the benzonium ion [C6H7](+), or the benzene radical cation, [C6H6](.+). As key-steps, these fragmentations contain reductive eliminations from the central As atom under H-H or C-H bond formation. Labeling experiments show that H/D exchange reactions precede these fragmentations and, specifically, that complete positional exchange of the H atoms in 1(.+) occurs. Computations at the UMP2/6-311+ G(d)//UHF/6-311+ G(d) level agree best with the experimental results and suggest: (i) 1(.+) rearranges (activation enthalpy of 93 kJ mol(-1)) to a distinctly more stable (Delta H-r(298) = -64 kJ mol(-1)) isomer 1 sigma(+) with a structure best represented as a distonic radical cation sigma complex between AsH and benzene. (ii) The six H atoms of the benzene moiety of 1 sigma(.+) become equivalent by a fast ring walk of the AsH group. (iii) A reversible isomerization 1(+) reversible arrow 1 sigma(.+) scrambles eventually all H atoms over all positions in 1(.+). The distonic radical cation 1 sigma(+) is predisposed for the elimination of an As atom or an AsH fragment. The calculations are in accordance with the experimentally preferred reactions when the As atom and the AsH fragment are generated in the quartet and triplet state, respectively. Alternatively, 1(.+) undergoes a reductive elimination of H2 from the AsH2 group via a remarkably stable complex of the phenylarsandiyl radical cation, [C6H5As](.+) and an H-2 molecule.

In order to reach a deeper insight into the reaction mechanism of the zeolite catalyzed methanol to hydrocarbons reaction (MTH), the proposed reaction intermediates, i.e., a series of multiply methyl-substituted benzenium ions has been generated in the gas phase by chemical ionization. The fragmentations of the corresponding long-lived (metastable) ions have been investigated. While expulsion of H2 dominates for the lower homologues, elimination of methane dominates for the higher homologues, accompanied by increasing amounts CH 3 · . Loss of larger fragments relevant to the MTH-reaction, in particular ethene, propene and even butene, is also observed in minor amounts. This latter finding is consistent with a proposed reaction cycle in the MTH reaction known as the paring mechanism, and the feasibility of this mechanism has thus been demonstrated. The metastable gas-phase ions studied here are considerably more energetic than those residing in a zeolite catalyst, but they were found to decompose with markedly higher selectivity towards alkenes as compared to those activated by collision-induced dissociation (CID).

Two examples of artificial supramolecular host-guest systems derived from resorc[4]arenes (calix[n]arenes based on resorcinol) and ammonium ions as guests have been studied by atomic force microscopy (AFM). For the first time, real single-molecule events have been determined for this type of supramolecular complexes and off-rates as well as molecular parameters of single-molecule aggregates such as the depths of the binding pocket (molecular length parameter) could be measured by applying the methods of dynamic force spectroscopy. In addition, this technique was also applied to differentiate between the two states (open and closed) of a photoswitchable resorc[4]arene-anthracene tweezer. An investigation of the exchange rates of various complexes in the gas phase by means of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry confirmed the results of the AFM study.